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Background The objective of this study was to describe the perspective of patients with early breast cancer toward research biopsies. The authors hypothesized that more patients at academic sites than at community‐based sites would be willing to consider these procedures. Methods In total, 198 patients with early stage breast cancer were recruited from 3 academic centers (n = 102) and from 1 community oncology practice (n = 96). The primary objective was to compare the proportion of patients willing to consider donating excess tissue biospecimens from surgery, from a clinically indicated breast biopsy, or from a research purposes‐only biopsy (RPOB) between practice types. Results Most patients (93% at academic sites, 94% at the community oncology site) said they would consider donating excess tissue from surgery for research. One‐half of patients from academic or community sites would consider donating tissue from a clinically indicated breast biopsy. On univariate analysis, significantly fewer patients from academic sites would consider an RPOB (22% at academic sites, 42% at the community site; P = .003); however, this difference was no longer significant on multivariate analysis (P = .96). Longer transportation times and unfavorable prior experiences were associated with less willingness to consider an RPOB on multivariate analysis. Significantly fewer patients from academic sites (14%) than from the community site (35%) would consider a research biopsy in a clinical trial (P = .04). Contributing to scientific knowledge, return of results, and a personal request by their physician were the strongest factors influencing patients' willingness to undergo research biopsies. Conclusions The current results rejected the hypothesis that more patients with early breast cancer at academic sites would be willing to donate tissue biospecimens for research compared with those at community oncology sites. These findings identify modifiable factors to consider in biobanking studies and clinical trials., In this study of the willingness of patients with early stage breast cancer to consider biospecimen collection procedures for the purposes of research, most patients were willing to provide blood samples for research but were less likely to consider percutaneous breast biopsies. Longer travel time to the clinic and adverse experiences with prior biopsies, but not treatment center type (academic versus community‐based center), were associated with less willingness to consider research biopsies.

Background. Tissue from research biopsies provides access to insights into tumor biology. We aimed to determine medical oncologists’ (MOs’) attitudes toward research biopsies in patients with metastatic breast cancer (MBC). Materials and Methods. A total of 309 breast MOs from National Cancer Institute (NCI)-designated cancer centers were invited to complete a self-administered survey about their attitudes toward approaching patients for research purpose-only biopsies (RPOBs), performed as a standalone procedure, or additional biopsies, performed with a clinically indicated biopsy. The MOs were asked to predict what proportion of their MBC patients would consider undergoing research biopsies. Results. Of the 309 MOs, 221 (72%) responded. Of these 221 MOs, 30 were ineligible, leaving 191 eligible responders. Nearly all the MOs reported they were comfortable approaching patients regarding research biopsies of blood or skin. One fifth of MOs were uncomfortable approaching patients for RPOBs of the breast. One half of MOs were uncomfortable approaching patients for RPOBs of the liver. A significant variation was found in the perceptions by MOs of their patients’ willingness to undergo research biopsies. The factors associated with increased comfort in approaching patients for research biopsies included fewer years in practice, caring for patients who had undergone recent research biopsies, and the predicted willingness of patients to consent to biopsies. The risk of a biopsy and biopsy-related pain were the most common reasons for reluctance to refer patients for research biopsies. Conclusion. Significant variation exists, even at NCI centers, in the comfort level of MOs in approaching MBC patients for research biopsies. MOs’ attitudes toward research biopsies might be a modifiable factor in increasing tissue collection for research. Implications for Practice: Tissue-based research is critical in advancing our understanding of cancer biology, and obtaining tissue from a research biopsy provides an essential resource. This study demonstrates the variability of oncologists’ attitudes toward research biopsies and elicits factors associated with increased comfort levels with approaching patients for research biopsies. Biopsy risk and biopsy-related pain were commonly cited reasons not to refer patients for research biopsies. If the risk of a research biopsy is deemed sufficiently low enough to be acceptable, oncologists’ attitudes might be a potential target for education and change, which may assist in increasing the availability of tissue for cancer research.

Background: Patients (pts) with breast cancer treated with neo-adjuvant therapy on clinical trials are often asked to consent to pre-treatment and on-treatment research biopsies. There is increasing interest in obtaining tissue samples at similar time points in pts treated with neo-adjuvant therapy outside of clinical trials. However, medical oncologists’ (MOs) attitudes towards approaching pts about research biopsies in this setting are unknown. Methods: Three hundred and nine academic breast MOs identified from websites of the National Cancer Institute (NCI) – designated cancer centers were asked to complete a survey either by paper or online. Eligible MOs (MOs who saw breast cancer pts and who saw pts >4 hours/week.) were asked to predict what proportion of their pts with newly diagnosed, non-metastatic breast cancer would consent to research purposes only biopsies (RPOBs) i.e., biopsies with no clinical benefit to pt. Median values are reported. Two-sided Fisher’s exact test was used to compare categorical variables using a α level of .05. Results: Of 221 (101F,85M, 5 unknown) MOs who completed the survey, 30 MOs were ineligible (response rate=221/309,72%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 14%, 63% and 21% of their pts would definitely/probably, maybe, probably not/definitely not consent to a RPOB of the breast. Forty-one percent, 34%, 19%, 3% of MOs were very comfortable, somewhat comfortable, somewhat uncomfortable, and very uncomfortable asking pts to consent to RPOBs respectively. The only factor associated with increased comfort discussing an RPOB was MOs’ years in practice. MOs with fewer years (15 years) (Adjusted RR=1.2, p =0.02). Gender, number of pts enrolled onto clinical trials, and MOs with pts who had research biopsies in the last 3 months was not associated with increased comfort. MOs who were more comfortable in approaching pts for RPOBs were associated with estimating a larger proportion of their pts as willing to undergo RPOB. For example, nearly one third of MOs who were very comfortable with approaching pts for RPOBs estimated that greater than 50% of their pts would consent to research biopsies. In contrast, nearly all the MOs who were very uncomfortable with approaching pts for RPOBs estimated that less than 25% of their pts would consent to research biopsies. The 3 most common reasons why MOs were reluctant to consent pts for a RPOB include pain/discomfort of a biopsy (59%), risk of a biopsy procedure complication, (44%), and inconvenience to the pt (33%). Conclusions: Academic breast MO’s predicted that fewer than 1 in 5 women with newly diagnosed, non-metastatic breast cancer would definitely or probably agree to a request for an RPOB outside of the context of a therapeutic trial, and approximately one-quarter of MOs expressed discomfort in approaching pts for such procedures. Our results have important implications regarding the feasibility of such research efforts, and identify potential barriers to target for intervention. Citation Format: Davinia SE Seah, Sarah Scott, Hao Guo, Julie Najita, Ruth Lederman, Elizabeth Frank, Jessica Sohl, Zsofia Stadler, Stuart G Silverman, Jeffrey Peppercorn, Eric P Winer, Steve E Come, Nancy U Lin. Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-17-01.

Background: Breast cancer is the second most common cancer associated with brain metastases. For some patients, central nervous system (CNS) progression is the primary clinical problem, and the optimal management of these patients remains a challenge. In this study we examined the differences in clinical characteristics, the features of CNS-directed therapy, and outcomes among breast cancer patients with brain metastases according to tumor subtype. Methods: A retrospective series of 214 breast cancer patients with brain metastases treated at the Dana-Farber Cancer Institute from 1999-2011 was identified. Tumor subtype was classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). Descriptive analysis was performed; Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used to compare clinical characteristics, CNS-directed therapy features, and outcomes between groups. Results: Median follow-up time since CNS progression was 8 months (0-117). Median age at CNS diagnosis was 52 years (30-82). Tumor subtype distribution was as following: 35% HR+, 36% HER2+, and 29% triple negative. Table 1 represents the clinical characteristics, CNS-directed therapy features, and outcomes according to tumor subtypes. More patients with triple negative disease (32%) had CNS involvement at presentation of metastatic disease. 8% of HER2+ patients had CNS as the only site of disease. A higher proportion of patients with HER2+ disease received more than one modality of CNS directed treatment as initial therapy. These patients also received more lines of CNS-directed therapy during the entire course of their disease. The median survival time after CNS progression differed by subtype; patients with HER2+ disease had the longest median survival times. Conclusions: Tumor subtype appears to impact clinical presentation, type and number of CNS-directed therapies, and survival among patients with breast cancer with brain metastases. Table 1 Tumor subtype HR+ (n = 74, 35%)HER2+ (n = 78, 36%)Triple negative (n = 62, 29%)P-valueBreakdown of treatment periods 0.2011999-200334%45%29% 2004-200628%17%31% 2007-201138%38%40% Clinical features at CNS disease presentationCNS disease at presentation of metastatic disease,%1522320.052Only site of metastatic disease,%181 Time from metastatic disease until CNS disease (median, min-max; months)16 (0-113)12 (0-65)6 (0-60) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-09.

Background: There is increasing interest in studying tissue from patients (pts) with metastatic breast cancer (MBC). Historically, limited tissue has been available. Possible barriers to research biopsies (bx) include pt and provider opinions; the contribution of each factor is unknown. Methods: 309 academic breast medical oncologists (MOs) identified from the websites of each of the National Cancer Institute - designated cancer centers were invited to complete either a self-administered paper or online survey. Eligible MOs (MOs who saw breast cancer pts and who saw pts 4 hours/week.) were asked to predict what proportion of their pts with MBC would consent to additional bx (ABs, additional bx performed with a clinically indicated bx) or research purposes only bx(RPOBs, research bx performed as a standalone procedure). They were also asked about their comfort levels in asking pts with MBC to consider participating in ABs or RPOBs for various organs. Median values are reported. Two-sided Fisher's exact test was used to compare categorical variables using a a level of .05. Results: 191 (101F,85M, 5 unknown) eligible MOs completed the survey. 29 MOs were ineligible (response rate = 191/280,68%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 90%, 75%, 70% and 50%, of their pts would definitely/probably consider ABs of blood, skin, breast, or liver respectively. MOs predicted that 90%, 60%, 33%, and 20% of their pts would definitely/probably consider RPOBs of blood, skin, breast, or liver. 98% (95% CI 96%-100%), 96% (95% CI 92%-98%), 93% (95% CI 88%-96%) and 70% (95% CI 63%-77%) of MOs were very/somewhat comfortable asking pts for an AB of blood, skin, breast and liver respectively. 98% (95% CI 95%-99%), 93% (95% CI 89%-96%), 78% (95% CI 72%-84%) and 50% (95% CI 43%-58%) of MOs were very/somewhat comfortable asking pts to participate in a RPOB of blood, skin, breast and liver respectively. No demographic characteristics (eg. sex, age) were associated with MOs’ comfort levels of asking pts to have an AB of blood, skin and breast. Factors associated with increased comfort discussing an AB of the liver were: age < 50 years (p = 0.01), in practice for < 15 years (p = 0.01), ≥ 1 pt enrolled on clinical trials per month (p = 0.02), or having pts who had undergone bx for research in prior 3 months (p MOs with ≥ 4 patients enrolled on clinical trials/month or whose pts had undergone research bx in the past 3 months were more likely to feel comfortable asking pts to have a RPOB of the breast (p The 3 most common reasons why MOs were reluctant to refer pts for participation in an AB include risk of a bx procedure (n = 128, 67%), pain/discomfort of a bx (n = 125, 65%), and logistical barriers (n = 42, 22%). These reasons are similar for RPOB; risk of a bx procedure, (n = 137, 72%), pain/discomfort of a bx (n = 134, 70%), and inconvenience to pt (time involved, travel, etc) (n = 58, 30%). Conclusions: Many MOs predict that the majority of their MBC pts will consider ABs of various organs. However, this decreases with RPOBs, particularly as the procedure becomes more invasive. More research is needed to understand factors that may influence MOs’ comfort levels asking pts to participate in such studies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-19-01.

Background Trastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable. Methods 113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan–Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model. Results Median OS was 3.5 years (95% CI 3.0–4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1–5.9, liver/lung: 3.2 years CI 2.5–4.2, other: 4.6 years CI 2.7–8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months. Conclusions The natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.

Background: In the era of molecularly targeted therapy, developing an understanding of the molecular basis of cancer is a principal or secondary goal of many research studies. For this reason, studies collecting tissue for research purposes are increasingly common. Understanding patients' attitudes towards research biopsies may lead to improvement in accrual to research biopsy studies. Methods: Patients with metastatic breast cancer from two academic and two community hospitals completed a self-administered paper survey consisting of 29 questions in clinic to evaluate their willingness to consider providing additional biopsies (additional biopsy performed with a clinically indicated biopsy) and research purposes only biopsies (RPOB) (research biopsy performed as a stand alone procedure). Results: 160 patients (n = 80 academic, n=80 community) completed the survey, with a response rate of 98%. As expected, demographic variables differed between sites, with patients from academic sites likely to be younger (p = 0.01), more educated (p = 0.002), employed (p = 0.01), have prior trial participation (P In univariate analyses of patients' willingness to have additional biopsies, patients in academic sites were more likely to agree to additional biopsies than those at community sites (RR = 1.2, 95% CI 1.0–1.5, p = 0.03). Statistically significant differences based on demographic characteristics such as age, education, marital status, prior trial participation, number of prior biopsies, and travel time were not observed. For RPOB, patients having had more prior biopsies were less likely to consider research biopsies (RR = 0.6, 95% CI 0.4–1.0, p = 0.03). The following variables did not reach statistical significance: type of practice, age, education, marital status, prior trial participation, and travel time. Patients' willingness in both academic and community sites to consider RPOB declined with more invasive biopsies. Although differences were observed, none were statistically significant between academic and community; skin (56%, 65%), bone marrow (30%, 27%), breast (43%, 49%) or liver (24%, 19%). Of the 13/160 (8%) patients who would not consider additional biopsies, the most common reasons cited included pain or discomfort (n = 8/13, 62%), risk of biopsy (n = 8/13, 62%) and anxiety related to the biopsy (n = 6/13, 46%). Of the 37/160 (23%) patients who would not consider RPOB, the most common reasons cited included pain or discomfort (n = 23/37, 62%), risk of biopsy (n = 15/37, 41%) and inconvenience of the procedure to the patient (n = 13/37, 35%). Conclusions: The majority of patients in this study indicated they would consider research biopsies, with a larger proportion willing to consider additional biopsies; patients seen at academic hospitals were more likely to consider additional biopsies compared to those seen at community hospitals. Breast cancer patients' willingness to undergo research biopsies may be higher than generally expected by clinicians and may not be the primary barrier to obtaining research biopsies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-16-04.

Background: HER2-positivity is a predictor of benefit from trastuzumab (TRZ), but fails to depict the observed interpatient variability in terms of treatment (tx) duration. In this study we described the relationship between clinicopathological features and TRZ tx duration. Methods: A retrospective consecutive series of 343 HER2+ breast cancer (BC) patients (pts) treated with TRZ at the Dana-Farber Cancer Institute from 1999–2008 was identified. 139 pts treated with 1st line TRZ-based tx were selected for analysis. Pts who received any non-TRZ prior tx for metastatic disease were excluded. TRZ tx duration was defined as time from start of 1st line therapy to the 1st day of 2nd line therapy or death. Central nervous system (CNS) progression with TRZ maintenance was not considered change of tx. Pts were divided equally into 3 groups based on the duration of 1st line tx distribution. Short-term responders (STR) were on the 1st line tx for 15m. An additional group of extremely LTR (ELTR) was defined as being in the 90th percentile of tx duration (>37m). Descriptive analysis was performed; fisher exact test, Kruskal-Wallis and logistic regression methods were used to compare groups. Results: Median follow-up time since metastatic diagnosis was 4 years (y) (range 0–11). Median age at diagnosis was 47y (22–83), 25% of stage I-III pts at diagnosis received adjuvant/neoadjuvant TRZ. The median disease free interval (DFI) was 20m (0–172), median number of metastatic sites was 2(1–5), 68% of pts had visceral disease. Median duration of 1st line tx was 10m (2–105). TRZ was given with CT in 86%, hormone tx in 6% and as monotherapy in 9%. 25% of pts developed CNS progression and continued tx. There were only small absolute differences for clinicopathological characteristics among STR, IR and LTR. ELTR had a median 1st line TRZ tx duration of 49m (37–105) and similar clinicopathological features to LTR. A higher proportion of LTR had hormone receptor (HR)-positive disease compared with STR, however no significant association between LTR and STR was found for HR status, DFI and visceral involvement. Conclusions: TRZ tx duration varies widely in the 1st-line advanced setting. No clinicopathological features were associated with TRZ tx duration. Our results suggest that despite CNS progression some pts continue to have long term benefit to TRZ tx. A major research priority is to identify molecular predictors of benefit and resistance to anti-HER2-based therapies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-03.

INTRODUCTION: As systemic therapy improves, brain metastases are increasingly common in patients with breast cancer. Unfortunately, effective therapy with durable control has remained elusive [1]. Combining bevacizumab and cyototoxic chemotherapy is an appealing approach as the anti-angiogenic effect of bevicizumab may improve delivery of cytotoxic drugs to brain tumors. METHODS: We conducted a Phase II study of patients with parenchymal brain metastasis treated with bevacizumab and carboplatin [2]. Patients could have any hormone receptor status or any number of prior therapies. Patients with HER2+ breast cancer also received trastuzamab. Correlative perfusion MRI scans to look at tumor perfusion, blood volume, vessel calibers and relative oxygen saturation (ΔSO2) levels were performed at baseline, day 1, and after 2 months of therapy [3, 4]. For consistency, the largest contrast-enhancing lesion in each patient visible on all three MR visits was selected for analysis. RESULTS: Thirty-eight patients were enrolled in the study of which 32 had, paired evaluable imaging datasets. Compared to baseline, 12/32 patients were identified as responders by a durable increase in ΔSO2 levels at day 1 and at 2 months above a 5% measurement error threshold. The remaining patients were identified by stable (15/32) or reduced (5/32) ΔSO2 levels. Patients responding to therapy showed increased tumor perfusion (Mann-Whitney; P10 µm) were seen across all patients. CONCLUSIONS: Similar to primary brain tumors [2, 3], perfusion MRI demonstrates that anti-angiogenic therapy can induce vascular normalization in a subset of patients with metastatic breast cancer to the brain. Our data indicate that the vascular response may also be associated with improved survival. [1] Lin NU, Lancet Oncol 2013 [2] Sorensen AG, Cancer Res 2012 [3] Emblem KE, Nat Med 2013

Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P

Background The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. Patients and Methods A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. Results At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR] positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (OR adjuvant trastuzumab vs. no adjuvant trastuzumab = 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699. Conclusion Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.

Background Research studies involving human tissue are increasingly common. However, patients' attitudes toward research biopsies are not well characterized, particularly when the biopsies are carried out outside the context of therapeutic trials. Patients and methods One hundred sixty patients with metastatic breast cancer (MBC) from two academic (n = 80) and two community (n = 80) hospitals completed a 29-item self-administered survey to evaluate their willingness to consider providing research purposes only biopsies (RPOBs) (as a stand-alone procedure) and additional biopsies (ABs) (additional needle passes at the time of a clinically indicated biopsy). Results Eighty-two (51%) of 160 patients would consider having RPOBs, of which 42 (53%) and 40 (50%) patients were from academic and community hospitals, respectively. Patients who had more prior biopsies were less likely to consider RPOBs (RR = 0.6, 95% CI: 0.4–1.0, P = 0.03). Of 160 patients, 115 (72%) patients would consider having ABs. Of these, 64 (80%) and 51 (64%) patients from academic and community hospitals, respectively, would consider ABs (RR = 1.2, 95% CI: 1.0–1.5, P = 0.03). Conclusions Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies.

The purpose of the current study was to characterize the outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence.Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified.The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death.Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed.

TPS668 Background: As a single agent, eribulin is associated with prolonged overall survival compared to treatment of physician’s choice in pts with heavily pre-treated metastatic breast cancer (MB...

513 Background: The anti-tumor and anti-edema effects of BEV provide a rationale for testing in BCBM. Carboplatin (C) is associated with CNS responses across multiple tumor types. We evaluated BEV + C in pts with BCBM. Methods: Pts with progressive, measurable BCBM (>/= 1 cm in longest dimension) were eligible. Cycle 1: BEV 15 mg/kg on Day 1, followed on Day 8 by carboplatin AUC=5 (plus trastuzumab if HER2+). In subsequent cycles, pts received BEV + C on Day 1 (plus trastuzumab if HER2+) of a 3 week (wk) cycle. Standard brain MRI was obtained at baseline (BL) and every 2 cycles. Non-CNS scans (CT or MRI) were performed after 2 cycles, 4 cycles, then every 4 cycles. Correlative brain imaging was obtained at BL, 12-96 hours after the first dose of BEV, and after 2 cycles. Circulating tumor cells and blood for VEGF polymorphisms were also collected. The primary endpoint was composite CNS objective response rate (CNS ORR). CNS partial response required all of the following: >/= 50% reduction in volumetric sum of target CNS lesions compared to BL, no progression of non-target lesions, no new lesions, stable/decreasing steroid dose, no progressive neurologic signs or symptoms, and no progression of non-CNS disease by RECIST 1.0. The study used a 2-stage design to distinguish between ORR 5% vs 20% (responses in >/= 1/12 pts to enter 2ndstage; responses in >/= 4/37 pts needed to be promising). Results: 38 pts were enrolled between 11/3/09-8/24/12 (30 HER2+; 8 HER2-negative). Most (76%) pts had received >/=2 lines of metastatic chemotherapy. 97% of pts with HER2+ disease received prior trastuzumab; 73% had prior lapatinib. All but 5 pts progressed after WBRT and/or SRS. As of 1/15/13, 3 pts remain on protocol therapy; 22 patients have died. The composite CNS ORR was 63% (95% CI 46%-78%). CNS ORR by RECIST was 45%. CNS responses were observed in both HER2+ and HER2-negative pts. Of 34 pts with >/= 24 wks potential follow-up time, median number of cycles was 8 (range 1-19). One grade 2 CNS hemorrhage event was reported; there were no cases of grade 3/4 CNS hemorrhage. Conclusions: BEV + carboplatin is associated with a high rate of durable CNS response in pts with BCBM. Updated results, including progression-free and overall survival will be presented. Clinical trial information: NCT01004172.

6089 Background: Benefits of CT vary widely in MBC pts. We aimed to describe the impact of breast cancer TS and line of tx on the duration of CT. Methods: In a retrospective analysis, we identified 205 pts treated with CT for MBC at the Dana-Farber Cancer Institute between 2005-8. TS were classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (TN) (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). CT duration was defined as "time from start of one CT line to the start of the next CT." Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used. Results: Median follow-up was 54 months (m). Most pts had received adjuvant tx, though 23% had MBC at diagnosis. Almost all HER2+ pts had concurrent anti-HER2 tx. CT duration was longest in 1st line with consecutive stepwise decrease. The proportion of pts who received CT beyond the 3rd line varied by TS: 52% of HER2+ pts received > 4 CT lines, compared with 37% of HR+ and 29% of TN pts. Duration in later CT lines also differed by TS. Median CT duration in HER2+ pts was > 4 m in all 6 lines, but HR+ and TN pts had a median CT duration of 6m of CT in 5th and 6th line; by contrast, CT duration for TN pts were consistently brief in later CT lines. Conclusions: TS determines the likely duration and number of lines of CT for MBC. Among HR+ and HER2+ pts who receive CT beyond 3rd line, there are substantial rates of prolonged tx suggesting clinical benefit. For TN pts, the opportunity for additional lines and the CT duration declined more dramatically. The true role of advanced (> 3rd) CT lines for all MBC in improving quality of life, survival, and the predictors of such benefit, warrant further study. [Table: see text]

e11100 Background: Trastuzumab (T) is associated with improvements in overall survival (OS) among patients (pts) with HER2+ MBC; however disease course in individual pts is highly variable. We aime...

e17574 Background: There is active debate concerning the ethics and risks of non-clinically indicated biopsies (bxs) in patients (pts) with cancer. In this analysis we examined our single institution experience regarding acceptance, safety, and success rate with research biopsies in pts with breast cancer (BC). Methods: An IRB-approved ongoing prospective study at the Dana-Farber Cancer Institute collects research bxs from pts with BC. Research bxs are performed as additional passes at the time of a clinical bx (cohort 1) or as a separate procedure for banking purposes only (cohort 2) on known tumor or suspicious lesions. Bxs are not linked to a specific therapeutic or correlative trial. Bx-site related risks are pre-specified in consent forms. Grade 2-5 adverse events (AEs) associated with the procedure are prospectively collected. Chart review for bxs between 2005-2013 was performed in this analysis. Results: As of January 2013, 158 pts had consented to the study; 3 pts withdrew consent and 4 pts did not have bxs. 151 pts are in the analytic cohort (total bxs performed= 161); 82% in cohort 1, 18% in cohort 2. Most pts were white (89%) with a performance status of 0-1 (98%). A majority of pts (96%) underwent a bx in the setting of known or suspected metastatic disease. 39% of bxs were performed at time of diagnosis or first recurrence. The most common sites for bx were liver (38%, n=61), skin (24%, n=39) and breast (18%, n=29). Lung was uncommon (3%, n=4). Research biopsies were successfully performed in 114 (92%) pts in cohort 1 and 27 (100%) pts in cohort 2. In cohort 1, research biopsies were not successful in 10 pts. In 9 pts the clinical samples had insufficient material, leading to the forfeit of the banked research sample for clinical purposes; in 1 pt the bx was suspended for severe pain. Only 3 (1.9%) pts had AEs ≥ grade 2: 1 with grade 2 pain; 1 with grade 2 pneumothorax; and 1 with grade 3 pain. Conclusions: Our experience in an academic medical center suggests that pts with BC are willing to undergo research bxs outside the context of a therapeutic or translational trial. These procedures can be performed safely with a high rate of successful tissue collection. Additional data are needed to fully quantify the risks and to demonstrate the value of these procedures.